Diepstra, A.

Franssen, C. F. M.

Wiegersma, J. S.

English

Lupus nephritis, a well-known complication in systemic lupus erythematosus, is characterised by a proliferative glomerulonephritis or membranous nephropathy along with a full-house immunofluorescence pattern on renal biopsy. There are very few exceptions in which similar histopathological findings are present, but case reports show that an increasing number of HIV-positive patients (mostly black Africans, but also white patients) have HIV-immune complex disease (HIVICK), which can mimic lupus nephritis. Lupus-like HIVICK is treated differently than 'true' lupus nephritis, so distinction is warranted.</p

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   University of GroningenNephrotic syndrome due to lupus-like glomerulonephritis in an HIV-positive patientWiegersma, J. S.; Franssen, C. F. M.; Diepstra, A.Published in:The Netherlands Journal of MedicineIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2017Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Wiegersma, J. S., Franssen, C. F. M., & Diepstra, A. (2017). Nephrotic syndrome due to lupus-likeglomerulonephritis in an HIV-positive patient. The Netherlands Journal of Medicine, 75(9), 412-414.http://www.njmonline.nl/getpdf.php?id=1912CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 14-02-2023412N O V E M B E R  2 0 1 7 ,  V O L .  7 5 ,  N O .  9© Van Zuiden Communications B.V. All rights reserved.The Netherlands Journal of MedicineC A S E  R E P O R TNephrotic syndrome due to lupus-like glomerulonephritis in an HIV-positive patientJ.S. Wiegersma1*, C.F.M. Franssen1, A. Diepstra2Departments of 1Nephrology, and 2Pathology, University Medical Centre Groningen, Groningen,  the Netherlands, *corresponding author: email: jankewiegersma@hotmail.comA B S T R A C TLupus nephritis, a well-known complication in systemic lupus erythematosus, is characterised by a proliferative glomerulonephritis or membranous nephropathy along with a full-house immunofluorescence pattern on renal biopsy. There are very few exceptions in which similar histopathological findings are present, but case reports show that an increasing number of HIV-positive patients (mostly black Africans, but also white patients) have HIV-immune complex disease (HIVICK), which can mimic lupus nephritis. Lupus-like HIVICK is treated differently than ‘true’ lupus nephritis, so distinction is warranted. K E Y W O R D SHIV immune complex kidney disease, HIV-associated nephropathy, HIVAN, HIVICK, lupus-like glomerulonephritisC A S E  R E P O R TA 26-year-old Caucasian female was referred to our centre for a second opinion. A few weeks earlier, she was admitted to another hospital with malaise, generalised weakness and peripheral oedema of the lower extremities. Medical history included perinatal asphyxia and pulmonary embolism without an apparent cause (at the age of 24 years). On physical examination, she was hypertensive (blood pressure 150/114 mmHg) and had severe oedema in both legs. Physical examination was otherwise unremarkable. Serum creatinine was elevated (table 1) and urinalysis showed glomerular erythrocyturia with 30-50 erythrocytes per high power field with < 1% acanthocytes and a few erythrocyte casts. Proteinuria was 13.1 g/24 hours. The differential diagnosis consisted of membranous nephropathy (including lupus), membranoproliferative glomerulonephritis or IgA nephropathy. A kidney biopsy showed active, diffuse and global lupus nephritis class 4/5 with endocapillary and mesangial proliferation and few sclerotic lesions. Immunofluorescence staining was positive for IgA, IgG, IgM, light chain type lambda and kappa and C1q/C3 (figure 1), Congo red was negative. Electron microscopy was not performed. Additional screening for ANA, ENA, and anti-DNA was negative; a weak cryoglobulin type 3 was detected along with a low complement factor C3 (0.69 g/l; normal 0.90-1.8 g/l) and normal C4 (0.21 g/l; normal 0.10-0.40 g/l).Except for a dubious facial rash and pancytopenia (without haemolysis) there were no other criteria for systemic lupus What was known on this topic?HIV infection is associated with various nephropathies, with HIV-associated nephropathy (HIVAN) being the most common. After introduction of combination antiretroviral therapy, the epidemiological spectrum of HIV-associated renal pathology has changed with a relative decrease of HIVAN and an increase of drug-induced tubular disease, HIV-immune complex kidney disease and HIV-associated comorbidities such as hepatitis C, diabetes mellitus and hypertension. What does the case add?Although nephrotic syndrome is a well-known manifestation in HIV-positive patients, it is mostly associated with HIVAN. Nephrotic syndrome due to lupus-like glomerulonephritis is far less common. Furthermore, this is the first case where lupus-like glomerulonephritis was the presenting manifestation of HIV infection. This case report also shows that antiretroviral treatment, together with antiproteinuric medication, may have a marked favourable effect on proteinuria and renal function. 413N O V E M B E R  2 0 1 7 ,  V O L .  7 5 ,  N O .  9The Netherlands Journal of Medicineerythematosus. The negative ANA and anti-DNA was also inconsistent with lupus disease, so another underlying disease was sought. Additional investigation revealed an HIV-1 infection with a viral load of 1.52*106 copies/ml and CD4 count 0.13*109/l (reference range 0.4-1.3*109/l). Serology for hepatitis B and C was negative. Antiviral therapy was started (dolutegravir, abacavir and lamivudine) in combination with antiproteinuric drugs (furosemide and enalapril). Along with a favourable virological response, renal function improved and the nephrotic syndrome went into partial remission (table 1).D I S C U S S I O NThe most common HIV-associated nephropathy is focal segmental glomerulosclerosis (known as HIV-associated nephropathy, HIVAN), which was first reported in the USA in 1984. It is characterised by nephrotic range proteinuria, renal dysfunction and collapsing focal segmental glomerulosclerosis, due to direct viral infection of renal cells or the action of viral proteins.1 Without combination antiretroviral therapy (cART) renal function often rapidly progresses to end-stage renal disease. Treatment with cART is therefore considered mandatory.2 Due to the introduction of antiretroviral treatment, the incidence of HIVAN has decreased. This has changed the epidemiological spectrum of renal pathology associated with HIV, with a relative increase in other nephropathies such as HIV-immune complex kidney disease, cART-induced tubulotoxicity and HIV-associated comorbidities such as hepatitis C virus infection, diabetic nephropathy and nephrosclerosis.1,3-5 Thrombotic microangiopathy and amyloid A amyloidosis are less frequently seen, but are also associated with HIV and kidney disease. HIVICK is characterised by the presence of glomerular and mesangial immune deposits and consists of a broad spectrum of histopathological entities such as membranous nephropathy and lupus-like nephritis.5 According to the literature, patients with HIVICK generally have less advanced HIV infection, usually have only mild proteinuria and less frequently progress to end-stage renal disease compared with HIVAN.5,6 In retrospective case series of HIV-positive patients, HIVICK is found in about 4-30% in renal biopsies (mostly reported as membranous nephropathy, and only rare cases described as lupus-like nephritis).1,4,6 However, selection bias may have underestimated the true incidence of HIVICK. The pathogenesis of HIV infection in immune complex renal disease is poorly understood, and treatment is also less obvious. Most patients with immune complex kidney disease are already treated with cART, but for those who have not yet received antiretroviral therapy, such as this patient, treatment may have beneficial effects on renal outcome.1,5-10 Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are often prescribed in order to control blood pressure and proteinuria, with a few case reports that report prescribing immunosuppressive therapy.5,10-12 More literature on pathogenesis, treatment and outcome is warranted in this upcoming renal disease. Wiegersma et al. Lupus nephritis in an HIV-positive patient.Figure 1. a) PAS staining of a representative glomerulus. Endocapillary proliferation consists of the presence of neutrophils and lymphocytes and endothelial cell enlargement. There is mesangial proliferation and a small sclerotic lesion. b) Immunofluorescence studies demonstrate mesangial and membranous staining in the characteristic ‘full house’ pattern, i.e. positive staining for all immune reactants (IgA, IgG, IgM, C1q, C3, kappa and lambda light chains)414N O V E M B E R  2 0 1 7 ,  V O L .  7 5 ,  N O .  9The Netherlands Journal of MedicineWiegersma et al. Lupus nephritis in an HIV-positive patient.D I S C L O S U R E SThe authors declare no conflict of interest. No funding or financial support was received.R E F E R E N C E S1. Rosenberg AZ, Naicker S, Winkler CA, Kopp JB. HIV-associated nephropathies: epidemiology, pathology, mechanisms and treatment. Nat Rev Nephrol. 2015;11:150-60.2. Lucas GM, Ross MJ, Stock PG, et al. Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect. Dis. 2014;59:96-138. 3. Haas M, Kaul S, Eustace JA. HIV-associated immune complex glomerulo-nephritis with ‘lupus-like’ features: a clinicopathologic study of 14 cases. Kidney Int. 2015;67:1381-90. 4. Wearne N, Swanepoel CR, Boulle A, Duffield MS, Rayner BL. The spectrum of renal histologies seen in HIV with outcomes, prognostic indicators and clinical correlations. Nephrol Dial Transplant. 2012;27:4109-18.5. Booth JW, Hamzah L, Jose S, et al. Clinical characteristics and outcomes of HIV-associated immune complex kidney disease. Nephrol Dial Transplant. 2016;0:1-9. 6. Foy MC, Estrella MM, Lucas, et al. Comparison of risk factors and outcomes in HIV immune complex kidney disease and HIV-associated nephropathy. Clin J Am Soc Nephr. 2013;8:1524-32.7. Szczech LA, Gupta SK, Habash R, et al. The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection. Kidney Int. 2004;66:1145-52.8. Matignon M, Lidove O, Dupuis E, Walker F, Abqrall S, Papo T. A lupus-like glomerulonephritis following acute HIV-1 seroconversion in an African woman. Nephrol Dial Transplant 2005;20:438-40.9. Sraer JD, Peraldie MN. Human immunodeficiency virus infection and acute renal insufficiency. Bull Acad Natl Med. 1997;181:17631779.10. Silva GEB, Leite VA, Salgado-Filhoh, et al. Necrotizing arteritis in a human immunodeficiency virus-infected patient with lupus-like glomerulo-nephritis. Int J Clin Exp Pathol. 2014;7:464-7. 11. Yang J, Seo MY, Kim KT, et al. A case of lupus-like glomerulonephritis in an HIV patient with nephrotic range proteinuria, purpura and elevated IgA level. Int J Clin Exp Pathol. 2014;7:4467-72. 12. Yoon JH, Chun SH, Shin JY, et al. A case of lupuslike glomerulonephritis in an HIV-infected patient. Infect Chemother. 2009;41:362-5.Table 1. Laboratory resultsAt presentation After 1 year Normal rangeSerumHaemoglobin (mmol/l) 6.0 9.2 7.5-9.9Leucocytes (109/l) 3.3 10.3 4.0-11.0Lymphocytes (109/l) 0.99 NA 0.8-3.2Thrombocytes (109/l) 110 348 150-350Haptoglobin (g/l) 1.4 0.3-2.0 CRP (mg/l) 16 NA < 10 Albumin (g/l) 13 43 35-50 Creatinine (μmol/l) 152 90 60-110 eGFR (ml/min/1.73 m2) 40 76 > 90 ANA Neg NAAntiDNA (IU/ml) 1 NA 0-15ANCA Neg NACryoglobulin Weak* NAComplement C3 (g/l) 0.69 NA 0.75-1.40 Complement C4 (g/l) 0.21 NA 0.10-0.34 UrineProtein (g/24h) 13.1 0.9Creatine clearance (mL/min) 40 118Selectivity index 37% NACRP = C-reactive protein; eGFR = estimated glomerular filtration rate; ANA = antinuclear antibodies; AntiDNA = anti double stranded DNA; ANCA = Anti-neutrophil cytoplasmic antibodies; NA = not applicable. *a weak mixed cryoglobulin was detected (type III; polyclonal IgG).

Nephrotic syndrome due to lupus-like glomerulonephritis in an HIV-positive patient

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Nephrotic syndrome due to lupus-like glomerulonephritis in an HIV-positive patient

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